Chronic stroke

Sagittal (side) view of the brain illustrating TGFα intracranially
infused into the brain containing a chronic stroke


TGFα is able to diffuse and reach the ependymal and subependymal zones of the brain, where it stimulates "quiet" adult stem cells and induces them to divide into massive numbers of new progenitor cells. The new cells migrate to zones of damage in the brain.

Cross section of the brain illustrating how TGFα acts to repair
damage in the brains of animal models with chronic stroke


RIGHT: key brain structures involved, including the striatum, the pallidum, the thalamus, and the midbrain dopamine neurons of the substantia nigra-ventral tegmental area.

LEFT: the cortical-striatal pallidal-nigral-thalamic-cortical "loop" is shown. In chronic stroke, all the neurons in the central (umbra) stroke area die.

TGFα infused into the stroke area of the striatum, pallidum, and/or cortex induces the adult stem cells lining the ependymal and subventricular zone adjacent to the striatum to divide (proliferate) in great numbers. This creates hundreds of thousands to millions of new progenitors, which then migrate to the regions of the striatum, pallidum, and/or cortex where they differentiate into neurons that have the appropriate brain area markers: striatal, pallisal, or cortical. The replacement of these new neurons is associated with dramatic improvement in sensorimotor and motor behavior.

Fluorescence photomontage of a cross section of the left side
of a rat's brain


The green-labeled cells at right are the new progenitor and adult stem cells. They have divided along the ependymal and subventricular zones lining the ventricle adjacent to the striatum, which appears as a black area peppered with clusters of green progenitors migrating toward the stroke lesion at the lower left. The stroke lesion also contains newly formed progenitor cells stained red and green, which have migrated from the subventricular zone at right. Connecting this zone and the site of the healing stroke site is an area of migrating green progenitors. Thus, the adult stem cells migrate from upper right to lower left. TGFα was injected into the brain area overlapping the stroke site.